BACKGROUND: In advanced non-small cell lung cancer (NSCLC), leptomeningeal metastases (LM) is a common consequence with rapid progression and a poor prognosis. LM affects roughly 3% to 5% of NSCLC patients, and it affects as many as 9.4% of individuals with epidermal growth factor receptor (EGFR) mutations. Cerebrospinal fluid cytology is the gold standard for diagnosing LM, while conventional cytopathology has a positive detection rate of less than 50%, resulting in a delay in diagnosis and treatment of LM. The fixation treatment of cerebrospinal fluid samples has a significant impact on the positive cytology detection rate, and how to improve the positive cytopathology detection rate of cerebrospinal fluid is a hot topic in clinical research. METHODS: From June 2019 to November 2021, 105 cases diagnosed with LM based on clinical symptoms and positive imaging were collected and retrospectively evaluated in the second ward of the Department of Oncology of The Second Affiliated Hospital of Harbin Medical University. The effect of different fixation methods on the positive rate of cerebrospinal fluid cytopathology was investigated, and specimens of cerebrospinal fluid were collected and sent for examination using different delivery methods, including the application of the TIB cell preservation solution kit (experimental group) and the routine application of sterile plastic tubes in lumbar puncture bags (control group). Biochemical assays (glucose and total protein) were performed on the cerebrospinal fluid fluid, and Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the supplementary diagnostic value for LM patients with lung cancer. The relevance of chemical indexes in the assessment of therapeutic efficacy was examined, and biochemical (glucose, total protein) indices and cytological changes in cerebrospinal fluid fluid after pemetrexed intrathecal injection therapy were dynamically monitored. RESULTS: In the control group, 24 (45.28%) patients were positive for the first time, while 42 (80.77%) patients were positive for the first time and 10 (19.23%) patients were negative for the first time in the experimental group. Significant differences existed between the two groups (P<0.001). The results of Logistic regression analysis of patients with the first cerebrospinal fluid biochemical test showed that the risk of positive cerebrospinal fluid biochemical pathology with less than 2.5 mmol/L was 2.456 times greater than 2.5 mmol/L of cerebrospinal fluid glucose (OR=2.456, P<0.05), and total cerebrospinal fluid biochemical protein greater than 430 mg/L was 2.647 times less than 430 mg/L (OR=2.647, P>0.05). The ROC curve showed glucose sensitivity of 76.9% in cerebrospinal fluid, the specificity of 54.5%, Youden index of 0.315 and area under the curve (AUC) of 0.620, total protein sensitivity in cerebrospinal fluid of 44.4%, 90.6%, Youden index of 0.350 and AUC of 0.671. After 2 cycles of pemetrexed intrathecal treatment with complete cerebrospinal fluid cytology and cerebrospinal fluid biochemical (glucose, total protein) tests in 73 and 50 patients, respectively, the rate of cerebrospinal fluid cytology turning negative was gradually increased. Cerebrospinal fluid glucose levels increased after 2 cycles of treatment compared with the first time, with a statistically significant difference (P<0.001). CONCLUSIONS The use of a cell preservation solution kit to immediately fix cerebrospinal fluid samples following isolation in patients with clinical symptoms and positive imaging greatly enhances the rate of positive cerebrospinal fluid cytology detection. The effect of treatment can be assessed and predicted by continuous dynamic monitoring of cerebrospinal fluid biochemistry and cytology.
Humans ; Lung Neoplasms/pathology* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Pemetrexed/therapeutic use* ; Retrospective Studies ; Meningeal Carcinomatosis/secondary* ; Glucose/therapeutic use*

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/drug therapy* ; Meningeal Carcinomatosis/drug therapy* ; Pemetrexed ; Treatment Outcome

Leptomeningeal metastases (LM), a special type of metastasis in advanced lung cancer, is known for its severe clinical symptoms, rapid progression and poor prognosis. LM used to be featured with low clinical diagnosis rate, limited treatment options, poor treatment efficacy, and very short survival if treatment not given. Though cerebrospinal fluid (CSF) cytology remains to be the gold standard for the diagnosis of LM, the positive rate of the first CSF cytology even in patients with suggestive clinical symptoms and positive imaging generally does not exceed 50%, leading to a delay in the diagnosis and treatment of patients with LM. With the progress of targeted therapy for driver gene-positive lung cancer and immunotherapy for driver gene-negative lung cancer, the overall survival of patients with lung cancer has been prolonged, meanwhile incidence of LM has been increasing year by year. Current clinical research in this field center around how to improve diagnosis rate and to find effective treatment approaches. This paper reviews advances in diagnosis and treatment of LM of lung cancer..
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Humans ; Lung Neoplasms/therapy* ; Meningeal Carcinomatosis/secondary* ; Meningeal Neoplasms/therapy* ; Treatment Outcome

BACKGROUND: To evaluate the efficacy of modified ventriculolumbar perfusion (VLP) chemotherapy with methotrexate on leptomeningeal carcinomatosis in terms of symptomatic response and side effects. METHODS: Previous infusion rate of 20 mL/h was reduced to 15 mL/h for the purpose of decreasing constitutional side effects of VLP such as nausea/vomiting, insomnia and confusion. The primary outcome was the response rate of increased intracranial pressure (ICP), and the secondary outcome was the occurrence of side effects compared to previous 20 mL/h trial. This interim analysis to validate the reduced infusion rate is not to affect the original effect of VLP chemotherapy. RESULTS: All forty-seven patients were enrolled including 22 patients with increased ICP. Thirteen patients out of these (59%) got normalized ICP after VLP chemotherapy. Moderate to severe (grade 2–3) confusion was observed in 3 patients (6%) and it was significantly reduced compared to those (23%) in the VLP 20 mL/h (p=0.017). Grade 2–3 nausea/vomiting was also reduced from 64% to 45% but failed to reach statistical significance (p=0.08). Median overall survival (OS) was 5.3 months (95% confidence interval, 3.55–7.05) and patients OS, who received maintenance VLP was significantly prolonged compared to patients who underwent induction VLP only (5.8 vs. 3.4 months, p=0.025). CONCLUSION: VLP of reduced perfusion rate (15 mL/h) showed compatible control rate of increased ICP at this interim analysis. Decreased moderate to severe side effects and prolonged OS in patients received maintenance VLP encourage us to evaluate the effectiveness of this trial further.
Drug Therapy ; Humans ; Infusions, Intraventricular ; Intracranial Pressure ; Meningeal Carcinomatosis ; Methotrexate ; Perfusion ; Sleep Initiation and Maintenance Disorders

BACKGROUND: Leptomeningeal metastasis (LM) is an uncommon, but devastating complication of advanced cancer and has no standard treatment. Herein, we analyzed the clinical characteristics and outcomes of patients with solid tumors who were diagnosed with LM. METHODS: Between January 2007 and December 2017, we retrospectively analyzed the medical records of patients with solid tumors who were diagnosed with LM. RESULTS: A total of 58 patients were enrolled in this study. The median age of patients was 51 years (range, 27–72 years), and 62.1% had a poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) (>2). The common types of primary tumor were breast cancer (39.7%), gastric cancer (25.9%), and non-small cell lung cancer (20.7%). Forty-two patients (72.4%) were diagnosed with LM by MRI of the brain and/or spine and cerebrospinal fluid (CSF) analysis, 14 were diagnosed by CSF analysis alone, and 2 were diagnosed by MRI alone. Treatments for LM were performed in 53 patients (91.4%), and best supportive care was provided for 5 patients (8.6%). Intrathecal chemotherapy, radiotherapy, and systemic chemotherapy were administered in 43 (74.1%), 17 (29.3%), and 24 (41.4%) patients, respectively. The median overall survival of the entire cohort was 2.4 months (95% confidence interval, 1.0–3.7). In the analysis of prognostic factors for survival, a good ECOG PS (≤2), administration of systemic chemotherapy after LM diagnosis, and a prior history of brain radiation were associated with prolonged survival. CONCLUSION: Although the prognosis of LM in patients with solid tumors is poor, systemic chemotherapy might improve survival in selected patients with a good PS.
Brain ; Breast Neoplasms ; Carcinoma, Non-Small-Cell Lung ; Cerebrospinal Fluid ; Cohort Studies ; Diagnosis ; Drug Therapy ; Humans ; Magnetic Resonance Imaging ; Medical Records ; Meningeal Carcinomatosis ; Neoplasm Metastasis* ; Prognosis ; Radiotherapy ; Retrospective Studies* ; Spine ; Stomach Neoplasms

OBJECTIVE: The purpose of this pilot study was to examine the safety and function of the newly developed cerebrospinal fluid (CSF) reservoir called the V-Port.METHODS: The newly developed V-Port consists of a non-collapsible reservoir outlined with a titanium cage and a connector for the ventricular catheter to be assembled. It is designed to be better palpated and more durable to multiple punctures than the Ommaya reservoir. A total of nine patients diagnosed with leptomeningeal carcinomatosis were selected for V-Port insertion. Each patient was followed up for evaluation for a month after the operation.RESULTS: The average operation time for V-Port insertion was 42 minutes and the average incision size was 6.6 cm. The surgical technique of V-Port insertion was found to be intuitive by all neurosurgeons who participated in the pilot study. There was no obstruction or leakage of the V-Port during intrathecal chemotherapy or CSF drainage. Also, there were no complications including post-operative intracerebral hemorrhage, infection and skin problems related to the V-Port.CONCLUSION: V-Port is a safe and an easy to use implantable CSF reservoir that addresses problems of other implantable CSF reservoirs. Further multicenter clinical trial is needed to prove the safety and the function of the V-Port.
Catheters ; Cerebral Hemorrhage ; Cerebrospinal Fluid ; Drainage ; Drug Therapy ; Humans ; Intracranial Pressure ; Meningeal Carcinomatosis ; Neurosurgeons ; Pilot Projects ; Punctures ; Skin ; Titanium

The incidence of leptomeningeal dissemination (LMD) of anaplastic glioma has been increasing. LMD can be observed at the time of initial presentation or the time of recurrence. As a result of both rarity and unusual presentation, a standard therapy has not yet been suggested. In contrast to leptomeningeal carcinomatosis for systemic solid cancers, a relatively prolonged survival is observed in some patients with LMD of anaplastic gliomas. Treatment modalities include whole craniospinal irradiation, intra-cerebrospinal fluid (CSF) chemotherapy, and systemic chemotherapy. In some cases, response to temozolomide (TMZ), with or without combined radiation has been reported. Here, we report two cases of LMD of an anaplastic glioma. In one case LMD presented at the time of diagnosis, and in the other at the time of recurrence after radiation. CSF cytology was positive in both cases, and persisted in spite of intrathecal methotrexate chemotherapy. Later, TMZ was prescribed for progressing brain parenchymal lesions, and both radiological and cytological responses were obtained after oral TMZ treatment.
Brain ; Cerebrospinal Fluid ; Craniospinal Irradiation ; Diagnosis ; Drug Therapy ; Glioma* ; Humans ; Incidence ; Meningeal Carcinomatosis ; Methotrexate ; Recurrence

No abstract available.
Headache ; Meningeal Carcinomatosis* ; Papilledema*

PURPOSE: In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer. MATERIALS AND METHODS: Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not. RESULTS: With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM. CONCLUSION: WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.
Brain* ; Breast Neoplasms* ; Breast* ; Cerebrospinal Fluid ; Follow-Up Studies ; Humans ; Incidence ; Meningeal Carcinomatosis* ; Multivariate Analysis ; Neoplasm Metastasis* ; Radiotherapy* ; Retrospective Studies

PURPOSE: In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer. MATERIALS AND METHODS: Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not. RESULTS: With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM. CONCLUSION: WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.
Brain* ; Breast Neoplasms* ; Breast* ; Cerebrospinal Fluid ; Follow-Up Studies ; Humans ; Incidence ; Meningeal Carcinomatosis* ; Multivariate Analysis ; Neoplasm Metastasis* ; Radiotherapy* ; Retrospective Studies